Diagnostic performance of contrast-enhanced ultrasound and enhanced magnetic resonance for breast nodules

In the current study, we sought to evaluate the diagnostic efficacies of conventional ultrasound (US), contrastenhanced US (CEUS), combined US and CEUS and magnetic resonance imaging (MRI) in detecting focal solid breast lesions. Totally 117 patients with 120 BI-RADS category 4A-5 breast lesions were evaluated by conventional US and CEUS, and MRI, respectively. SonoVue was used as contrast agent in CEUS and injected as an intravenous bolus; nodule scan was performed 4 minutes after bolus injection. A specific sonographic quantification software was used to obtain color-coded maps of perfusion parameters for the investigated lesion, namely the time-intensity curve. The pattern of contrast enhancement and related indexes regarding the time-intensity curve were used to describe the lesions, comparatively with pathological results. Histopathologic examination revealed 46 benign and 74 malignant lesions. Sensitivity, specificity, and accuracy of US in detecting malignant breast lesions were 90.14%, 95.92%, and 92.52%, respectively. Meanwhile, CE-MRI showed sensitivity, specificity, and accuracy of 88.73%, 95.92%, and 91.67%, respectively. The area under the ROC curve for combined US and CEUS in discriminating benign from malignant breast lesions was 0.936, while that of MRI was 0.923, with no significant difference between them, as well as among groups. The time-intensity curve of malignant hypervascular fibroadenoma and papillary lesions mostly showed a fast-in/fast-out pattern, with no good correlation between them (kappa < 0.20). In conclusion, the combined use of conventional US and CEUS displays good agreement with MRI in differentiating benign from malignant breast lesions.     

Progress in development and application of the contrast-enhanced ultrasound quantitative analysis in perfusion imaging of the abdominal organs

Developments of contrast agent and imaging technique have made it possible for using contrast-enhanced ultrasound (CEUS) to assess perfusion. As an irradiative, real time and repeatable technique, ultrasound is revealing its advantages in this field compared with nuclear medicine, CT and MRI. This paper introduces the mechanism and methods of the CEUS in the perfusion ultrasound. The advancement in the study of the time-intensity curve (TIC) in systemic organs is also reviewed in this paper.     

基于因子分析法的超声肝灌注定量分析初步研究

局灶性肝结节(FLLs)通常可从超声造影图像序列中提取的时间强度曲线进行量化评价.为了克服人工选择的主观性并自动提取曲线,提出一种用于因子分析的基于顶点搜寻的替代-近似(RA)算法.该算法将高维图像序列映射到一维空间,先找到与生理结构对应的两个顶点.然后,根据这两个已知点的信息,在二维空间中可以寻找到第3个顶点.这3个顶点对应着3条不同的目标曲线.实验采用6个在患者自由呼吸运动下采集的肝细胞癌病例对RA算法进行验证.实验结果表明,此方法能准确提取到具有生理意义的因子曲线和相应的因子图,提取的因子曲线与感兴趣区域(ROI)测定曲线的平均相关系数值为0.91±0.03.初步证明了RA算法在FLLs灌注的量化分析具有可行性.     

基于S-G滤波的超声造影分析参数灌注成像

为弥补以往超声造影定量分析软件将感兴趣区(ROI)作为均质的整体区域进行分析的不足,提出一种基于S-G滤波器的在时域内直接处理数据平滑问题的定量分析方法,针对ROI区域内部像素点进行灌注成像参数分析,快速并可最大限度地保留原始有用信息。首先获得超声造影的原始DICOM动态医学数据,获取ROI内每个像素点的时间强度曲线,用S-G滤波器对时间强度曲线进行分析,得到反映灌注时相和灌注强度的多项定量分析参数,如到达时间(AT)、达峰时间(TTP)、达峰强度(PI)、平均通过时间(MTT)、曲线下面积(AUC)和上升斜率(RS)等;然后再对像素点参数分别进行彩色编码并以不同颜色显示,从而准确量化和直观显示超声造影的各项灌注参数。为评估该分析方法的稳定性,比较3位研究者分别对15个肝细胞癌病灶的分析结果。经统计,所有参数的组间相关系数(ICC)>0.80,验证了该方法的可行性和稳定性。     

动态CEUS-TIC定量分析对复发性小肝癌的诊断价值

目的:研究动态超声造影时间-强度曲线（CEUS-TIC）定量分析对复发性小肝癌的诊断价值。方法:选取接受肝癌切除术后的159例复发性小肝癌患者197个病灶,经病理确诊,患者均接受CEUS检查,以病理确诊结果为标准,分析恶性组和良性组CEUS参数以及各时相灌注模式等差异,并采用受试者特征曲线（ROC）分析动态CEUS-TIC定量参数对复发性小肝癌的诊断价值,计算敏感度、特异性和曲线下面积（AUC）。结果:CEUS显示良性病灶84个,恶性病灶113个,CEUS对恶性病灶诊断的准确率为85.61%（113/132）;恶性组始增时间、达峰时间、等增强开始时间以及低增强开始时间显著短于良性组（t=4.929, t=11.231, t=5.400, t=9.652, P<0.05）;两组动脉期不同时相分布比较,差异无统计学意义（Z=0.700, P>0.05）,恶性组门脉期高增强或等增强以及延迟期低增强比例显著高于良性组（Z=2.280, Z=2.160, P<0.05）;始增时间、达峰时间、等增强开始时间和低增强开始时间各参数联合诊断的特异度（92.30%）和AUC（0.942）高于各参数单一诊断的特异度（66.20%、75.40%、43.10%、84.60%）和AUC（0.767、0.808、0.710、0.838）。结论:动态CEUS-TIC定量分析对复发性小肝癌具有良好的诊断价值,是一种简单、可行的诊断复发性小肝癌的检查方法。 【关键词】肝癌;动态超声造影;时间-强度曲线;诊断价值     

A case of xanthogranulomatous cholecystitis preoperatively diagnosed with contrast-enhanced ultrasonography

We report a case of xanthogranulomatous cholecystitis (XGC) that was diagnosed preoperatively by means of ultrasonography (US) with the contrast-enhancement agent Sonazoid after a false-positive result had been obtained with fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET). A 69-year-old woman was admitted because of right upper quadrant pain. Blood tests revealed a serum CA19-9 level of 749.8 IU/L. Computed tomography (CT), US, and magnetic resonance imaging of the abdomen showed abnormal thickening of the gallbladder wall but no stones. The border between the gallbladder and the liver was unclear. FDG-PET revealed a lesion with increased uptake of tracer in the gallbladder wall. The thickness of the lesion was similar to that on CT. We suspected gallbladder carcinoma with hepatic invasion. To confirm the tentative diagnosis, we performed US with the contrast-enhancement agent Sonazoid. The gallbladder wall was homogeneously enhanced in the early vascular phase and remained enhanced for 90 seconds. Enhancement of the gallbladder wall was smooth and regular. The border between the gallbladder and liver was clear and smooth. On the basis of these examinations, we diagnosed chronic cholecystitis (XGC suspected), not gallbladder carcinoma. At surgery, the gallbladder wall was observed to be extremely thick because of severe inflammation, and cholecystectomy was performed. XGC was diagnosed on intraoperative pathological examination. Histopathological examination showed XGC, severe proliferative fibrosis with formation of multiple yellow-brown intramural nodules, and foamy histiocytes without malignant cells. In conclusion, the present case of XGC was diagnosed preoperatively with contrast-enhanced US after a false-positive result had been obtained with FDG-PET. Contrast-enhanced US can thus play important roles in diagnosing gallbladder disease and selecting treatment.     

Immunohistochemical detection of 8-hydroxydeoxyguanosine,a marker of oxidative DNA damage,in human chronic cholecystitis

Immunohistochemical detection of 8-hydroxydeoxyguanosine, a marker of oxidative DNA damage, in human chronic cholecystitis
Aims : Recent studies suggest that oxidative DNA damage induced during chronic inflammation may play a role in carcinogenesis in some organs. Although gallbladder carcinomas are frequently observed with a background of chronic cholecystitis, little is known about oxidative DNA damage in chronic cholecystitis. The aims of this study were to investigate the expression of 8-hydroxydeoxyguanosine (8-OHdG), a biomarker of oxidative DNA damage, in normal and chronically inflamed human gallbladder mucosa and compare its expression with clinicopathological findings.
Methods and results : 8-OHdG expression was immunohistochemically examined using a monoclonal antibody against 8-OHdG in human gallbladder specimens. In normal gallbladder ( n =5), no 8-OHdG expression was observed. In contrast, nuclear expression of 8-OHdG was detected in 28 of 31cases (90.3%) in gallbladder epithelial cells with chronic cholecystitis. The positive cells were predominantly observed in the areas of active inflammation with prominent cell infiltration. Quantitative analysis revealed that the number of 8-OHdG+ cells (labelling index) significantly ( r _s=0.671, P  < 0.05) correlated with the degree of the activity of mucosal inflammation, while gender, age, and the presence of gallstones did not influence the index.
Conclusions : Oxidative DNA damage is common in chronic cholecystitis, suggesting a possible link between chronic inflammation and gallbladder carcinogenesis.     

肝移植术后肝癌复发的超声造影与CT诊断比较

目的探讨超声造影（CEUS）对肝移植术后肝癌复发的诊断价值。方法对肝癌病人肝移植术后常规彩色超声随访发现肝内占位性病变23例，先行超声造影检查，3d内行螺旋CT增强扫描，分别与病理结果比较。结果23例病人经过穿刺活检病理确诊20例，行再次肝移植术经病理确诊3例，CEUS确诊18例，疑诊4例，误诊1例；CT确诊20例，疑诊2例，误诊1例。结论CEUS与CT对原位肝移植术后肝癌复发的诊断均很敏感且价值很高，尤其对不典型病灶的诊断，CT与CEUS结合能提高诊断率。     

LAM-1/Leu 8 antigen is expressed on portal, but not on lobular intrahepatic mononuclear cells in inflammatory liver disease.

The expression of the selectin receptor LAM-1/Leu 8 was analysed in normal and in inflamed liver tissue, and its expression on mononuclear inflammatory cells was correlated with their topographical distribution in various compartments of the inflamed liver, in order to obtain new insights on possible molecular mechanisms involved in the traffic of mononuclear inflammatory cells throughout the diseased hepatic parenchyma. In normal liver tissue, few scattered mononuclear cells in portal and lobular parenchyma corresponded to both CD4+ and CD8+, as well as to CD45RA+ (2H4+) naive and CD45RO+ (UCHL1+) memory T cells, and were LAM-1/Leu 8+. In acute and chronic inflamed liver biopsies, CD45RO+ (UCHL1+) CD4+ and CD8+ memory T cells largely predominated in both portal and lobular parenchyma. The expression of LAM-1/Leu 8 antigen on these memory T cells varied according to their localization in the liver parenchyma, and it was not correlated with specific aetiological causes. In acute hepatitis, the vast majority of T lymphocytes were LAM-1/Leu 8-. In chronic active hepatitis, memory T cells in portal tracts expressed LAM-1/Leu 8, whereas virtually all intralobular T cells accumulating in areas of periportal and intralobular inflammation were LAM-1/Leu 8-. In chronic persistent hepatitis, the LAM-1/Leu 8+ T cells largely predominated among the numerous mononuclear inflammatory cells within enlarged portal tracts, whereas LAM-1/Leu 8- T cells were restricted to areas of intralobular 'spotty' inflammation. Therefore, two phenotypical populations can be recognized among the memory T cells in inflamed liver tissue, according to their topographical localization: LAM-1/Leu 8+ T cells predominating in portal tracts, and LAM-1/Leu 8- T cells predominating in the lobular parenchyma. These data show that during their migration through the inflamed liver parenchyma, memory T lymphocytes undergo phenotypical changes (LAM-1/Leu 8 shedding) according to their localization in different liver compartments (portal tracts vs. lobular parenchyma), suggesting multiple cellular and molecular mechanisms involved in the regulation of the leucocyte traffic through inflamed liver tissue.     

Structural and metabolic characteristics of liver acini in dogs with acute cholecystitis

Structural and metabolic changes in liver tissue in dogs with acute cholecystitis were studied by histological, histoenzymatic, and biochemical methods. It was found that the development of destructive inflammatory processes in the gallbladder wall induces morphological damage to the liver tissue, which correlates with metabolic disorders in this organ and leads to liver dysfunction.     

胆囊皱襞位置异常与胆囊疾病关系的探讨

目的探讨胆囊皱襞异常与胆囊疾病的关系。方法我科1995年1月至2006年10月共发现5000例皱襞胆囊,根据其位置分为胆囊皱襞位置正常组（2500例）和胆囊皱襞位置异常组（2500例）,对其超声资料进行回顾性分析。结果位置正常组中正常胆囊占56%;病变胆囊44%,其中胆囊结石、慢性胆囊炎、慢性胆囊炎合并胆囊结石、急性胆囊炎、胆息肉、胆囊腺肌增生症的发病率分别为11.1%、9.2%、10.7%、8.4%、3.4%、1.1%。位置异常组中正常胆囊占12.1%;病变胆囊达87.9%,其中胆囊结石、慢性胆囊炎、慢性胆囊炎合并胆囊结石、急性胆囊炎、胆息肉、胆囊腺肌增生症的发病率分别为20%、8%、39%、12.9%、5.2%、2.8%。结论胆囊内由于皱襞位置异常,影响了胆汁的排泄及胆囊收缩功能,导致胆汁郁积,是胆囊疾病发生的病因之一,且皱襞越近底部或皱襞横贯性越大,胆囊疾病的发病率越高。     

Standardize and Compare Contrast-enhanced Ultrasonographic Digital Images Obtained with Different Technologies: How to Overcome the Subjectivity

Objective This study was conducted to compare digital images obtained with cadence contrast pulse sequencing (CPS) and coherent contrast imaging (CCI) technologies for contrast-enhanced ultrasonography (CEUS). Methods A CEUS study on 17 focal liver lesions was performed using CPS and CCI technologies with a second-generation contrast media. The lesion/liver ratio and conspicuity index were then calculated and compared with Adobe Photoshop 6.0. Results Lesion/liver ratio and conspicuity index using CCI ranged from 1.3 to 7.1 (mean value, 3) and 19 to 127 (mean value, 58), respectively; by using CPS, we obtained results ranging from 2 to 19.1 (mean value, 8.9) and 57 to 164 (mean value, 109.2). Lesion/liver ratio and the conspicuity index for the lesions using CPS showed significantly (p < 0.0001) superior results than those obtained using CCI. Conclusion The computed analysis with standardization allows an objective evaluation of digital images of CEUS. CPS technology resulted in better lesion conspicuity compared to CCI during CEUS study on focal liver lesions.     

Comparison of contrast-enhanced ultrasonography with grey-scale ultrasonography and contrast-enhanced computed tomography in diagnosing focal fatty liver infiltrations and focal fatty sparing

PurposeFatty liver infiltrations and fatty sparing impair diagnostic performance of grey-scale ultrasonography in differentiating malignant and benign focal liver lesions.In the study, we present our experience in diagnosing focal fatty liver infiltrations and focal fatty sparing with contrast-enhanced ultrasonography (CEUS) in comparison to grey-scale ultrasonography and contrast-enhanced computed tomography (CECT).Material and MethodThe retrospective study group (n=82 patients), included 44 (53.7%) men, 38 (46.3%) women (aged 29–81 years, mean 55.8 years) with 48 focal fatty liver infiltrations and 34 focal fatty sparing. All patients underwent grey-scale ultrasonography (US), CEUS using SonoVue^® and CECT executed within the 7 days.ResultsWith US, CEUS and CECT focal fatty liver infiltrations were diagnosed in 22, 46 and 44 cases, respectively. The following values were obtained: sensitivity ? 45.8%, 95.8% and 91.7%, specificity ? 100% for all, accuracy ? 95.2%, 99.6% and 99.3%, respectively. Focal fatty sparing was diagnosed in 16, 31 and 30 cases, respectively. The following values were obtained: sensitivity ? 47.1%, 91.2% and 88.2%, specificity ? 99.8%, 100% and 100%, accuracy ? 95.6%, 99.4% and 99.3%, respectively. No statistically significant differences were found in sensitivity of diagnosing focal fatty liver infiltrations and focal fatty liver sparing between CEUS and CECT. Sensitivity of grey-scale ultrasonography was significantly lower when compared to those of CEUS and CECT (p<0.001).ConclusionCEUS is as sensitive as CECT in focal fatty infiltrations and focal fatty sparing diagnosing. However, CEUS provides more information than CECT about the vasculature and enhancement pattern of focal fatty liver infiltrations.     

冠心病患者心肌声学造影定量分析的初步研究

拟探讨MCE定量分析在缺血性心脏病上的诊断价值。对10例临床诊断冠心病的患者行MCE,从时间-强度曲线中获得造影剂再灌注强度峰值(SIpeak),再灌注时间(Rt),再灌注率(b)和心肌血流量(SI×b)。同一检查对象不同心肌节段的4个参数(SIpeak、Rt、b和SI×b)均有统计学上的差异(P<0.05),对照组和观察组SIpeak具有统计学上的差异,SIpeak预测缺血性心脏病的ROC曲线下面积(AUC)为0.782,最佳临界值为64.4,以SIpeak≤64.4来预测缺血性心脏病,敏感性83.3%,特异性69.0%。利用超声造影匹配成像技术能够较满意地显示心肌灌注状态,初步研究表明通过MCE及Qontrast多参数定量分析软件可以评价心肌梗死区和缺血区的血流灌注缺损。SIpeak是预测缺血性心脏病的敏感指标。     

急性胆囊炎患者血浆β-防御素-3的检测及临床意义

目的:揭示急性胆囊炎患者血浆β-防御素-3浓度的变化,探讨其与急性胆囊炎患病危险性的相关性。方法:收集急性胆囊炎患者作为胆囊炎组,共82例,其中坏疽性胆囊炎15例,非坏疽性胆囊炎67例。收集同期健康体检者作为对照组,共50例。ELISA检测血浆β-防御素-3浓度。统计分析其与急性胆囊炎患病危险性的相关性。结果:t检验显示,胆囊炎组患者血浆β-防御素-3浓度(81.4±36.9)pg/ml显著低于对照组血浆β-防御素-3浓度(154.2±28.3)pg/ml(P<0.001),坏疽性胆囊炎患者血浆β-防御素-3浓度(64.2±24.1)pg/m1显著低于非坏疽性胆囊炎患者血浆β-防御素-3浓度(94.3±29.9)pg/ml(P<0.001)。Logistic回归分析显示,血浆β-防御素-3浓度是罹患急性胆囊炎(OR=0.483,95%CI=0.298～0.709,P<0.01)和坏疽性胆囊炎(OR=0.426,95%CI=0.239～0.648 P<0.01)的独立危险因素。ROC曲线分析显示,血浆β-防御素-3浓度预测罹患急性胆囊炎(曲线下面积=0.824,95%CI=0.712～0.896,P<0.001)和坏疽性胆囊炎(曲线下面积=0.836,95%CI=0.723～0.904,P<0.001)有显著预测价值。结论:急性胆囊炎患者血浆β-防御素-3水平降低,可能是急性胆囊炎的危险因素。     

Primary squamous cell carcinoma of gallbladder presenting as acute cholecystitis

Primary squamous cell carcinoma of gallbladder accounts for only 0-12.7% of all cases of gallbladder cancer. We here report a case of primary squamous cell carcinoma of gallbladder presenting as acute cholecystitis. A 50 year old man was admitted with the complaints of pain in right hypochondrium and fever of 2 days duration. Abdominal examination revealed tenderness along with guarding and rigidity in right hypochondrium with positive Murphy's sign. The patient was conservatively treated as a case of acute cholecystitis. After 12 hrs of unrewarding treatment patient was operated upon and cholecystectomy done. The specimen revealed thick walled gallbladder with multiple calculi. Histopathology revealed squamous cell carcinoma grade II.     

Gastric heterotopia in the gallbladder. Case report and review of literature.

We report a case of gastric heterotopia in the gallbladder of an 18-year-old man. Symptoms of acute cholecystitis are characteristic in patients under 20 years old, while older patients present with chronic cholecystitis and gallstones. The heterotopic mucosa results either in a mass, a polyp, or a multiloculated gallbladder. Twenty-eight other cases of gastric heterotopia in the gallbladder or cystic duct have been reported. In only three was it associated with peptic ulceration. Treatment is cholecystectomy. Heterotopic gastric mucosa has been described throughout the length of the gastrointestinal tract from the oral cavity to the rectum. Curiously, it is extremely rare in the gallbladder, where it has the propensity for causing symptoms of acute cholecystitis, particularly in the young. We report a case of this condition in which there was a separate loculus lined by gastric epithelium.     

超声造影定量分析对乳腺良恶性肿瘤区域血流动力学灌注特征的研究

目的研究乳腺良恶性肿瘤区域血流灌注的变化特点。方法乳腺良恶性肿瘤共60例,均为女性,年龄2270岁,平均年龄40岁。应用超声造影时间-强度曲线定量分析技术,检测其中乳腺恶性肿瘤30例（33个病灶）、乳腺纤维腺瘤30例（34个病灶）瘤灶边缘及中心部区域灌注参数峰值强度（PI）、曲线下面积（AUC）、达峰时间（TTP）、廓清时间（WOT）,用光学、透射电子显微镜观察瘤内新生血管显微结构及超微结构改变,免疫组织化学技术检测CD34、VEGF、Flk-1/KDR在两组肿瘤中的表达特性。结果恶性组病灶边缘各灌注参数与中心区域相比差异有统计学意义（P〈0.05）,良性组病灶边缘各灌注参数与中心区域相比差异无统计学意义（P〉0.05）。光学显微镜下恶性组90.91%（30/33）见坏死灶,血管异常丰富区位于癌巢边缘。良性组未见坏死灶,血管管径和分布均一。透射电子显微镜下恶性组新生血管内皮细胞超微结构具有不同于正常血管内皮细胞的分裂旺盛的瘤性特征,癌巢边缘可见扩张、迂曲的大血管,癌巢中心常见狭窄、闭塞的幼稚新生血管。恶性组瘤内微血管密度（MVD）显著高于良性组（P〈0.05）,尤其富集于癌巢边缘。VEGF及Flk-1/KDR在恶性组血管内皮细胞尤其是癌巢边缘呈强阳性表达,在良性组血管内皮细胞几乎不表达（P〈0.05）。结论实时超声造影区域灌注参数的差异为乳腺良恶性肿瘤的鉴别诊断提供了重要依据。针对VEGF或Flk-1/KDR为靶点进行新生血管特异性分子显像可能为乳腺癌的准确诊断提供新的思路,癌巢边缘可能是下一步进行乳腺癌分子影像观察的重点靶区。     

Acute surgical abdomen and myelofibrosis

Extramedullary hematopoiesis associated with fibrosis is found frequently in the liver and spleen, but seldom in other organs. Acute abdomen due to extramedullary hematopoiesis has been reported in two patients with intestinal obstruction because of heavy infiltration of the terminal ileum. This report describes the case of a 71-year-old woman with myeloid metaplasia involving the gallbladder mimicking acute cholecystitis. As far as we know, involvement of the gallbladder by extramedullary hematopoiesis has never been reported before.     

The effect of bactibilia on the course and outcome of laparoscopic cholecystectomy

Although bactibilia is an important condition of acute cholecystitis, its effect on the course and outcome of the infectious gallbladder disease has rarely been studied, particularly in relation to the laparoscopic procedure. The current study attempts to learn more about the inter-relationship between bactibilia and laparoscopic cholecystectomy during acute cholecystitis. Demographic, preoperative, operative, and postoperative data were prospectively collected in every patient with acute cholecystitis treated in the department of surgery at the Bnai Zion Medical Center, Israel. Intraoperative biliary samples were collected under aseptic conditions at the time of operation for bacteriologic examination and were routinely cultured in aerobic and anaerobic media for 3 days. The study population was divided into culture-positive and culture-negative groups, and the collected parameters were compared between the groups. Age over 60 years, a palpable gallbladder, temperature over 37.5 degrees C, a white blood cell (WBC) count of more than 12,000/cc(3), and serum alkaline phosphatase higher than 100 U/dL were all found to be factors capable of predicting bactibilia. Bactibilia was a significant factor associated with total, as well as infectious, operative complications. Bactibilia is considered to indicate an advanced stage of acute cholecystitis. In cases of laparoscopic cholecystectomy for infectious gallbladder disease, bactibilia is strongly associated with total, as well as local, infectious complications. Preoperative conditions such as older age, elevated temperature, a palpable gallbladder, elevated WBC count, and elevated serum levels of alkaline phosphatase can serve as predictors of bactibilia and its consequent complications. Although the sensitivity and specificity of the predictive factors for bactibilia are limited to 63% and 67%, respectively, in their presence during acute cholecystitis, conservative wide-spectrum antibiotics as the first-line therapy is appropriate, and, upon regimen failure, laparoscopic surgery by an experienced surgeon is indicated as the adjusted therapy.